Method for preventing and/or treating infections, colonisations, or illnesses related to staphylococcus aureus, pseudomonas aeruginosa, streptococcus pyogenes, enterococcus faecium, enterobacter cloacae, proteus mirabilis, bacteroides fragilis, staphylococcus epidermidis, propionibacterium acnes, candida albicans and/or malassezia furfur

ABSTRACT

The subject matter of the present invention is a bacterium or a mixture of bacteria having an antagonistic activity with respect to strains of  S. aureus, P. aeruginosa, Streptococcus pyogenes, Enterococcus faecium, Enterobacter cloacae, Proteus mirabilis, Bacteroides fragilis, Staphylococcus epidermidis, Propionibacterium acnes, Candida albicans  and/or  Malassezia furfur  as well as the use thereof in the treatment and/or prevention of infections or colonizations related to those pathogens. The invention pertains to care products containing one or more non-pathogenic antagonistic strains intended to prevent and/or treat infections or colonizations on skin, wounds, mucous membranes and appendages.

The present invention relates to bacteria having antagonist activities(hereinafter referred to as “antagonistic bacteria”) with respect topathogenic bacteria or yeasts belonging to the genera and speciesStaphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes,Enterococcus faecium, Enterobacter cloacae, Proteus mirabilis,Bacteroides fragilis, Staphylococcus epidermidis, Propionibacteriumacnes, Candida albicans and/or Malassezia furfur and to the use thereofas an active ingredient or in a medical device, in particular in thetreatment and/or prevention of colonization and/or infections related tothese pathogenic bacteria or yeasts. The bacteria which are antagonisticwith respect to pathogenic bacteria or yeasts have been selected fortheir abilities to inhibit the adhesion and the development and/or theproliferation of pathogenic bacteria or yeasts and thus to stabilizeand/or regulate the ecosystem. The invention relates to care productscontaining one or more non-pathogenic antagonistic strains intended forthe prevention or treatment of infections or colonizations on the skin,wounds, mucosae and superficial body growths.

Staphylococcus aureus and Pseudomonas aeruginosa are responsible for acertain number of pathological conditions, such as skin and mucosaeinfections, wound infections, in particular infections of chronic wounds(ulcers, diabetic wounds), burns and surgical wounds. These bacterialspecies are in particular known to be responsible for delayed healing.They are also involved in other pathological conditions, such asgastrointestinal, urinary and pulmonary infections, otitis or sinusitis.

Pseudomonas aeruginosa, otherwise known as pyocyanic bacillus, can,under certain conditions, be pathogenic. This very resistant bacteriumis, with other gram-negative bacteria, increasingly often involved innosocomial infections. This strain has the ability to become organizedas a biofilm, which makes it all the more resistant to antibiotics. Itis one of the most difficult bacteria to treat clinically. The mortalityrate reaches 50% in vulnerable (immunodepressed) patients. It is aubiquitous microorganism which is very resistant to numerousantiseptics, which is frequent in the hospital environment, and whichleads to the appearance (because of its resistance to antibiotics) ofactual hospital strains. It generates various forms of pathologicalcondition: eye infection, wound infection (especially burns and surgicalwounds), urinary infection (especially after catheters),gastrointestinal and lung infections (for example after bronchoscopy),inoculation meningitis, septicemia such as the terminal state of seriousinfections, or complication in patients subjected to animmunosuppressive treatment, leukemia patients, etc. It readily inducessystemic infections in individuals who are immunodepressed (because ofchemotherapy or by AIDS) and in burn victims and cystic fibrosisvictims.

Staphylococcus aureus is the most pathogenic species of theStaphylococcus genus. It is responsible for food poisoning, suppurativelocalized infections and, in certain extreme cases, physical septicemia(graft, cardiac prostheses). The species proves to be an opportunisticpathogen in certain locations or under certain circumstances. It is aubiquitous microorganism which has good resistance to naturalpurification mechanisms. S. aureus is also found in the commensal flora(in 15% to 30% of healthy individuals in the nasal fossae and thethroat, it can also be found in small amounts in the digestive tract andoften at the level of the perineum).

S. aureus has pathogenic capacities, in particular an invasive capacity,a capacity to multiply and to spread in the organism, and also a toxiccapacity. S. aureus has a great capacity for developingantibiotic-resistant mutants (by way of example, mention may be made ofmethicillin-resistant Staphylococcus aureus, or MRSA, which is one ofthe main causes of nosocomial infections). As a result, it shares, withpyocyanic bacillus, the primary role in infections of hospital origin.

These pathogenic bacteria and yeasts have the capacity to adhere tosurfaces and in particular to epithelial tissues and to develop in theform of biofilms in healthy or immunodepressed hosts. Biofilms aredefined as complex assemblies of microorganisms (or microbialcommunities) which adhere to a biotic surface (living tissues, skin,etc.) or an abiotic surface (inert material such as silicone or steel)and are trapped in a matrix of organic polymers (Costerton et al., 1999,Dunne, 2002). These biofilms may thus be monospecific, i.e. compounds ofa single bacterial or yeast species, or mixed when they are composed ofseveral bacterial or yeast species.

The common treatment for infections related to the presence ofpathogenic bacterial species is the use of antibiotics (penicillin,cephalosporin). However, the use of this approach presents a certainnumber of drawbacks:

-   -   these antibiotics often have a considerable spectrum of action        and may be responsible for an imbalance in terms of the        commensal flora, which may subsequently result in colonization        by pathogenic microorganisms;    -   the bacteria are capable of acquiring capacities of resistance        to these antibiotics;    -   the resistance of bacteria in the form of biofilms is greatly        increased compared with bacteria alone, also called planktonic        cells.

Faced with the problems of multiple resistances of pathogenicmicroorganisms to antibiotics, there is an urgent need to find analternative to this type of treatment.

One solution envisioned in order to prevent or treat infections ofbacterial or yeast origin is the use of bacterial strains which areantagonistic with respect to pathogenic species. The termbacteriotherapy is then used. These antagonistic strains are capable, byvirtue of their metabolism, of producing antimicrobial molecules and/orof interfering with the adhesion of pathogenic bacteria and yeastsand/or of disrupting cell communication between pathogenic bacteria andyeasts and/or of possessing angiogenic activities. They can also controlinflammation (immunomodulatory properties). These bacteria form apositive biofilm at the surface of the skin, wounds, mucosae orsuperficial body growths, which can take hold temporarily and limit theimplantation of pathogenic bacteria and yeasts.

This is particularly advantageous when the infection and/or thecolonization is located on the skin and/or in a wound.

These antagonistic strains generally belong to the family of lactic acidbacteria. These strains have been isolated from various matrices andmainly from feces. The activities of these strains are widely used forthe prevention and treatment of disorders at the level of the intestinalmucosa; the term probiotic bacteria is then used. Other applications atthe level of the mucosa of the ear, nose and throat and of theurogenital mucosa have also been described. By way of example, mentionmay be made of patent EP 871 503 which relates to a diaper or sanitarynapkin comprising microorganisms chosen from the genera Lactobacilluscurvatus, Lactobacillus plantarum or Lactococcus lactis havingantagonistic properties which allow them to combat strains ofundesirable microorganisms present or forming in the absorbent article,or in the urogenital zone. Patent application WO 99/53932 relates to acomposition for the treatment of otitis, comprising microorganismschosen from Streptococcus sanguis, Streptococcus oralis andStreptococcus mitis.

The applicant has particularly focused on the strains which areantagonistic with respect to the pathogenic strains S. aureus and P.aeruginosa.

One of the objects of the present invention also potentially consists increating a transient positive biofilm at the surface of the skin,superficial body growths, mucosae and/or wounds, which prevents orlimits the implantation of pathogens and the proliferation thereof.

The antagonistic bacteria according to the present invention areparticularly advantageous for use thereof in pathological conditionsinvolving the pathogenic species S. aureus and P. aeruginosa, such asgastrointestinal, urinary and pulmonary infections, otitis or sinusitis,wounds or pathological conditions involving colonization of wounds, ofthe skin, of superficial body growths or of mucosae.

The antagonistic bacteria according to the present invention areparticularly advantageous for use thereof in the various types of wounds(chronic, acute, burns), but also in skin conditions (such as, forexample, folliculitis, impetigo, eczema, boils, anthrax, whitlow,atopies, perleche, superinfections of lesions related to viruses such asthe herpes virus or the chickenpox virus).

Indeed, a wound is a lesion subsequent to a trauma, causing a loss ofskin or an opening of the skin. The healing process is set up inresponse to the formation of a wound.

The natural healing of a wound occurs mainly according to threesuccessive phases, each of these phases being characterized by specificcell activities which bring about the progression of the repair processaccording to precise chronological sequences: the inflammatory phase,the granulation phase (or proliferative phase), and the scar formationphase.

The rapidity and the quality of the healing of a wound depend on thegeneral condition of the affected organism, on the etiology of thewound, on the condition and the location of the wound, on the possibleoccurrence of an infection, and also on genetic factors possiblypredisposing to healing disorders. Tom or cut skin can no longer act asa barrier against microbes, which can then penetrate into the organism,causing an infection.

Bacteria and yeasts are inevitably present in wounds, this is naturalcolonization.

According to the amount of bacteria and/or of yeasts, the bacterialand/or yeast species present and the response of the organism, adistinction is made between colonization, local infection and infection.

Colonization is the presence of a certain amount of bacteria and/or ofyeasts within the wound without this leading to an inflammatoryresponse. After multiplication of the microorganisms on the wound, andadhesion thereof to epithelial cells, an equilibrium is establishedbetween the patient and the microbial flora thereof. The microorganismsremain at the surface of the wound and adhere thereto so as to form abiofilm. From a quantitative point of view, colonization ischaracterized by an amount of microorganism of less than 10⁵bactreria/mm³. If the amount of bacteria and/or of yeasts exceeds thisnumber, some authors cite critical colonization, then strictly localsuperficial infection in the presence of considerable bacterial and/oryeast colonization. This considerable presence of bacteria and/or ofyeasts is detrimental to the correct operating of the healing processand induces delayed healing.

The term “infection” will be used when the presence of the bacterialand/or yeast microorganisms leads to a locoregional inflammatoryresponse and the appearance of general signs with clinical signs whichreflect tissue invasion by the microorganisms present (large amount ofthe microorganisms present, bacterial virulence, decrease in immunedefense mechanisms of the patient). The infection is characterized bythe locoregional and general clinical signs.

Said infection can result in wound extension with exposure of underlyinganatomical structures such as ligaments or bones.Bacterial colonization does not require particular therapeuticapproaches, whereas an infection requires the setting up of local andgeneral antibacterial treatments.The infection is generally the determining factor in the non-healing ordelayed healing of wounds, directly or indirectly. Any bacterial and/oryeast contamination of a wound increases the inflammation.This may be beneficial in the case of moderate contamination (inevitablein the case of an open wound), but becomes deleterious in the case ofinfection of the wound which results in delayed healing.

Thus, the immediate complication of healing is first and foremost theinfection which prevents the initiation of the healing process frombeing set up; a wound is considered to be infected when the amount ofbacteria and/or yeasts present in the wound hinders the healing processor worsens the wound.

In this case, the healing, termed second intention healing, usuallyrequires the use of dermatological medicaments and of surgical tools(surgical knife, curette, etc.). In the case of a leg ulcer, forexample, it is necessary to disinfect the wound beforehand withantiseptics (such as chlorhexidine or hexamidine) and to clean thewound, which consists in removing the debris and the excess secretion,either by means of a surgical act or using proteolytic medicaments, i.e.medicaments of which the purpose is to destroy the strips of dead skinwhich contaminate the wound. Among the active agents commonly used fortreating wound infections, mention may also be made of silver, copper,octenidine, iodine, PHMB to (polyhexamethylene biguanide) and honey.

However, antibacterial agents and/or antiseptics are not recommended inwounds. The effectiveness of these active agents, from the viewpoint oftheir mechanisms of action, is short lived, they are inactivated byorganic substances, they may be cytotoxic with respect to cellcomponents, they have a broad spectrum, and, consequently, they will notonly attack the pathogenic bacteria, but will also destroy the commensalflora. Furthermore, a certain number of bacterial strains have developeda resistance to antiseptics/antibacterial agents.

There is therefore a need to have active agents which are effective inthe treatment and/or prevention of wound infections or colonizations bybacteria and/or yeasts, which are efficient, easy to use andnon-invasive.

One solution envisioned in order to prevent or treat infections orcolonizations of bacterial origin and/or due to yeasts at the level ofthe skin, wounds, mucosae and/or superficial body growths is the use ofbacterial strains which are antagonistic with respect to pathogenicstrains. These strains are capable, by virtue of their metabolism, ofproducing antimicrobial molecules and/or interfering with the adhesionof pathogenic bacteria and/or yeasts. These bacteria can also form apositive biofilm at the surface of the skin, the wound, the mucosae orthe superficial body growths, which can be established temporarily andlimit the implantation of pathogenic bacteria and/or yeasts.

These antagonistic strains generally belong to the family of lactic acidbacteria and/or have been isolated from the commensal flora of themucosae of human beings. The activities of these strains are widely usedfor the prevention and treatment of disorders at the level of theintestinal mucosa, of the ENT mucosa and of the vaginal mucosa. Suchstrains are described in WO 96/38159, WO 00/61201, EP 1 140 226, EP 1461 012 and WO 2006/013441.The antagonistic effect of these strains is due to various mechanisms,such as:

-   -   nutritional competition for carbonaceous and/or nitrogenous        substrates;    -   production of antimicrobial molecules, such as lactic acid,        hydrogen peroxide (H₂O₂), reducing molecules or bacteriocins;    -   adhesion competition for the binding sites on the mucosae        (barrier effect);    -   production of biosurfactants;    -   inhibition or disruption of cell communication between the        various bacterial species;    -   immunomodulatory activities enabling the stimulation of local        and systemic immunity.

The applications using probiotic strains on the skin and wounds alsogenerally make use of one of the activities previously described.

Mention may thus be made of applications concerning angiogenic effectsof probiotic strains of Lactobacillus acidophilus ATCC 4356 and ATCC43121, and Bacillus polyfermenticus, at the level of the skin and theintestinal mucosa (Halper et al., 2003, Im et al., 2009). Probioticstrains of Bifidobacterium longum reuter, of Lactobacillus paracaseiCNCM I-2116, of Lactobacillus johnsonii La1 and of Vitreoscillafiliformis, in topical forms, have also been used to regulateinflammation phenomena and dysregulations at the level of the skin(Gueniche et al., 2006, Gueniche et al., 2008a, Gueniche et al., 2008b,Gueniche et al., 2008c, Gueniche et al., 2008d, Gueniche et al., 2009,Gueniche et al., 2010). In the context of these applications, theauthors emphasize the immunomodulatory capacity of the strains. Suchstrains are described in patent applications EP 1 593 382 and WO2006/037922.

The use of a strain of Lactobacillus plantarum ATCC 10241 has beendescribed for limiting the growth of Pseudomonas aeruginosa and theformation of biofilms by this strain by releasing signal molecules whichdisrupt cell communication (or quorum sensing). The direct applicationof a piece of gauze impregnated with a culture of this strain, on burnmodels in rats and on human burns, has made it possible to demonstrateits effectiveness (Peral et al., 2009, Valdez et al., 2005). Theimmunomodulatory capacity of this strain with respect to neutrophils andleukocytes has also been exploited for treating chronic wounds (diabeticwounds, venous ulcers) and for reducing inflammation caused by P.aeruginosa (Peral et al., 2010, Ramos et al., 2010, Ramos et al., 2012).A formulation of this strain in an alginate film has been described byBrachkova et al. (Brachkova et al., 2011) for the prevention of burninfections by P. aeruginosa.

A strain of Lactobacillus fermentum RC-14 has demonstrated notablecapacities for inhibiting Staphylococcus aureus adhesion and limitinginfections related to this microorganism at the level of surgicalimplants (Gan et al., 2002). This antimicrobial effect has beenattributed to the release of a biosurfacant.

The effectiveness of several strains of Lactobacillus andBifidobacterium isolated from to different sources, in the preventionand treatment of methicillin-resistant Staphylococcus aureus, has alsobeen demonstrated in a study by H. Sikorska et al., 2013.

The inhibition of the growth of Staphylococcus epidermidis andPropionibacterium acnes by strains of Lactobacillus reuteri (KCTC 3594,KCTC 3678 and KCTC 3679) has been demonstrated (Kang et al., 2012).

The effect of the bacteriocins produced by Lactococcus sp. HY 449against inflammatory bacteria of the skin, such as Staphylococcusepidermidis ATCC 12228, Staphylococcus aureus ATCC 65389, Streptococcuspyogenes ATCC 21059 and Propionibacterium acnes ATCC 6919, has beendemonstrated (Ho et al., 2006).

Dressings or fabrics calling for the use of probiotic strains (lacticacid bacteria of Bacillus coagulans) have already been described (U.S.Pat. No. 7,025,974 and WO 2008/074331). The effectiveness of theseformulations is based solely on the use of bacterial strains capable ofproducing lactic acid as principal broad-spectrum antimicrobial agent.

The objective of the present invention is to provide novel active agentsbased on bacteria which are antagonistic with respect to the pathogenicbacteria Staphylococcus aureus and/or Pseudomonas aeruginosa, and whichare effective in the treatment and/or prevention of colonization and/orinfections related to these pathogenic bacteria, in particular at thelevel of the skin, wounds, mucosae and superficial body growths. Inaddition, these active agents can be administered directly in contactwith the skin, wounds, mucosae and superficial body growths, or caneasily be incorporated into compositions, in particular compositionssuitable for topical application, and are non-invasive.

In an innovative manner, the antagonistic bacteria have been preselectedon the basis of several criteria: (i) their capacities to inhibit thegrowth of pathogenic organisms, namely S. aureus and P. aeruginosa, (ii)their capacities to adhere and to form a positive biofilm on collagenand epidermis, (iii) their capacities to limit the adhesion ofpathogenic microorganisms on matrices containing collagen and (iv) theircapacities to limit the inflammatory reaction (TNF-α production bymacrophages).

These bacteria are capable of developing a barrier effect at the levelof the skin, wounds, mucosae and superficial body growths and thus ofpreventing and limiting the risks of colonizations and infections.

The inventors have been particularly interested in selecting strainswhich are antagonistic mainly with respect to the S. aureus and P.aeruginosa, which are the pathogenic species predominantly involved ininfections, in particular nosocomial infections.

Additionally, the inventors have selected bacterial strains which, inaddition to inhibiting strains of S. aureus and P. aeruginosa, inhibitthe development of other pathogenic species, such as Streptococcuspyogenes, Enterococcus faecium, Enterobacter cloacae, Proteus mirabilis,Bacteroides fragilis, Staphylococcus epidermidis, Propionibacteriumacnes, Candida albicans and Malassezia furfur. These microorganisms aremore particularly involved in wound and skin infections.

Propionibacterium acnes is an anaerobic gram-positive bacillus whichgrows relatively slowly and is normally present in the skin, the hairand the mucosae. It is responsible for acne.

The bacterium is widely present in the skin flora of most adults in goodhealth, but it is also responsible for post-operative infections, which,in particular in the case of the presence of an implant, are potentiallysevere: central nervous system infections, endophthalmitis,endocarditis, infections of the ENT and pulmonary sphere,spondylodiscitis, peritonitis and osteoarticular infections.

Staphylococcus epidermidis is a commensal bacterium of the skin invirtually 100% of human beings; its lipolytic properties allow it toprosper in sebum. It is normally harmless, but it causes authenticinfections in patients whose immune system is compromised or patientswho have catheters or prostheses. These may be dermatological infectionsand nasal infections, such as sinusitis or else urinary infections inwomen and more rarely in men. These bacteria have the capacity toproduce biofilms which allow them to adhere to the surfaces of medicalprostheses.

Candida albicans manifests itself differently according to its location.In immunocompetent patients (i.e. whose defense system is effective,unlike immunodepressed patients), it appears in the form of thrush inthe buccal cavity, redness and itching on the skin, essentially in thefolds, which are warm and moist areas favorable to the development ofyeast, and small local genital inflammations such as urethritis in humanbeings or vulvovaginitis with whitish discharge and itching in women.Malassezia furfur is a yeast involved mainly in seborrheic dermatitiswhich is a common inflammatory skin dermatosis (observed in 3% to 5% ofthe population). It presents in the to form of red plaques, covered withfatty and yellowish squamae, which are more or less prurigineous,predominant in the zones rich in sebaceous glands, the seborrheic zones.On the face, the topography of the lesions is suggestive: groovesbetween the nose and the lips, root of the eyebrows, scalp, wings of thenose, folds of the pinnae, concha of the ears, external auditory canals.On the scalp, frequent involvement results in a more or less seborrheicdandruff condition. On the trunk, two common zones are noted in humans:the sternum and the region between the two shoulder blades.It is encountered both in adults and infants (of less than 3 months), inwhom it manifests itself through the conventional “cradle cap” in thescalp and erythema on the buttocks. In adults, this pathologicalcondition is observed especially on subjects between 20 and 40 years ofage. Men are more frequently affected than women. In women, thedevelopment is observed more particularly at the time of the menopause.The pathological condition of multifactorial inflammatory origin is notcontagious and can evolve through attacks triggered most commonly bystress or pollution and a lack of sun.The cause is unknown, but a microscopic fungus is thought to play a rolein conditions likely to produce a particular immunoallergy.Pityriasis versicolor is a superficial mycosis, related to theproliferation on the skin of Malassezia furfur. This yeast normallylives at the surface of the skin, but, in certain situations, itmultiplies at great speed and causes these small brown or discoloredmarks.This fungus has a liking particularly for oily skin, lying on thethorax, but also on the neck and the shoulders, on the upper back and onthe upper limbs, rarely on the lower limbs.

A subject of the present invention is therefore a bacterium chosen fromthe strains of Lactobacillus saniviri also denoted in the presentapplication by F3C5p (registered on Jul. 12, 2012, under No. CNCM I-4650at the Collection Nationale de Cultures de Microorganismes [NationalCollection of Microorganism Cultures], Institut Pasteur, 25 rue duDocteur Roux, 75724 Paris Cedex 15, France, hereinafter denoted “CNCM”),Lactobacillus salivarius also denoted in the present application byF50C2p, F52C3p and F41C3p (registered respectively under Nos. CNCMI-4651, CNCM I-4652 and CNCM I-4653 at the CNCM), Streptococcus mitisalso denoted in the present application by F3C2v (registered on Jul. 12,2012, under No. CNCM I-4654 at the CNCM) and Lactobacillus pentosus orplantarum also denoted in the present application by L1C1 (registered onJul. 12, 2012 under No. CNCM I-4655 at the CNCM). These bacteria arecalled “bacteria according to the invention” in the present application.

A subject of the present invention is also a bacterium according to theinvention for use as an immunomodulator.

The subject of the present invention is also the use of such a bacteriumas an active ingredient or as a medical device or as a cosmetic or elseas a food supplement. The bacterium according to the invention may alsobe used as an active ingredient in a medicament, in a medical device, ina cosmetic or in a food supplement.

The present invention is also directed toward a bacterium according tothe invention for use in the treatment and/or prevention of colonizationand/or infections related to at least one bacterium or one yeast chosenfrom P. aeruginosa, S. aureus, S. pyogenes, E. faecium, E. cloacae, P.mirabilis, B. fragilis, Staphylococcus epidermidis, Propionibacteriumacnes, Candida albicans and Malassezia furfur.

Preferentially, the present invention is directed toward a bacteriumaccording to the invention for use in the treatment and/or prevention ofcolonization and/or infections related to P. aeruginosa and/or S.aureus.

The present invention relates more particularly to the treatment and/orprevention of wound and skin colonization and/or infections bypathogenic bacteria or yeasts.

The term “treatment” of or “treating” an infection or a colonizationmeans reducing and/or inhibiting the development of this infection orcolonization.

The term “prevention” of or “preventing” an infection or colonizationmeans reducing and/or avoiding the appearance of the symptoms of theinfection or colonization.

The expression “infection or colonization of wounds” is intended to meanan infection or a colonization chosen from diabetic foot ulcers, legulcers of arterial origin, leg ulcers of venous origin, bedsores,whitlow, infections related to acute wounds, infections related totraumatic wounds, such as wounds caused by severing, penetrating wounds,wounds caused by thermal or caustic agents and burns; and infectionsrelated to post-operative wounds, such as simple sutured wounds of asurgical incision, complex sutured wounds after skin excision, surgicaldermabrasions and non-suturable wounds requiring second-intentionhealing.

The bacterium according to the invention can be incorporated into acomposition, for instance a medical device. For the purposes of thepresent invention, the term “medical device” is intended to meanprostheses, catheters, dressings, ostomy bags, surgical drapes, urinarycatheters, endotracheal tubes, tympanostomy tubes, bandages, supportbandages, orthopedic and breast implants, contact lenses, intrauterinedevices, or else materials for sutures.

A subject of the present invention is also a composition comprising atleast one bacterium according to the invention. Said compositioncomprises, in an acceptable medium, at least one bacterium according tothe invention. The term “acceptable medium” is intended to mean a mediumthat is compatible with the skin, wounds, mucosae and superficial bodygrowths.

The composition according to the invention, or the bacterium accordingto the invention, may be administered topically, orally or parenterally.

Preferably, such a composition or such a bacterium is suitable fortopical application to the skin, wounds, superficial body growths ormucosae, such as the nose and throat, urogenital, digestive orrespiratory mucosa. The composition may thus be directly applied to theskin, wounds or mucosae.The term “topical application” is intended to mean application to theskin, wounds, mucosae and/or superficial body growths.

The composition according to the invention preferably comprises 10³ to10¹² bacteria, preferably 10⁶ to 10¹¹.

The topical composition may be in liquid, paste or solid form, and moreparticularly in the form of a salve, a cream, a milk, an ointment, apowder, an impregnated pad, a syndet, a wipe, a solution, a gel, aspray, a foam, a suspension, a lotion, a stick, a shampoo or washingbase. It may also be in the form of a suspension of microspheres ornanospheres or of lipid or polymeric vesicles or of microcapsules or ofa polymeric patch and a hydrogel for controlled release. Thiscomposition for topical application may be in anhydrous form, in aqueousform or in emulsion form.

The parenteral composition may be in the form of a solution forsubcutaneous injection (injectable solution).

The oral composition may be in the form of a solution, a powder, a gelcapsule or a tablet, or may be integrated into a food product, such as adairy product.

The bacterium according to the invention may be incorporated into thecomposition in the form of an inactivated cell, in particularinactivated by heat, by UV radiation or by any other process. It mayalso be incorporated in the form of a living cell which may beencapsulated or nonencapsulated, immobilized or nonimmobilized, andlyophilized or nonlyophilized, or else in the form of a cell extract. Itmay also be a cell lysate or any other type of presentation known tothose skilled in the art.

Preferentially, the antagonistic bacteria used in the context of thepresent invention, or a galenic formulation containing them, will beapplied directly to the wound, either in the form of a topicalcomposition, or integrated into a synthetic or nonsynthetic matrix whichis part of the composition of a dressing.

In this embodiment, the bacteria are formulated in a dressing, or elseformulated in a composition which is itself included in a dressing ormay be included at the time of application of the dressing. The dressingaccording to the invention therefore comprises at least one bacteriumaccording to the invention, or at least one composition according to theinvention.

The antagonistic bacteria according to the invention or the compositionsaccording to the invention containing them may be incorporated into anycomponent of the structure of a dressing, with the proviso that saidbacteria can directly or indirectly come into contact with the surfaceof the wound.

Preferably and in order to promote a rapid action, the bacterium (or acomposition according to the invention containing it), will beincorporated into the layer of the dressing which comes into contactwith the wound, or will be deposited on the surface of the dressingwhich comes into contact with the wound.

Advantageously, the bacterium (or a composition according to theinvention containing it) may thus be deposited, in a continuous ordiscontinuous manner, on the surface intended to come into contact withthe wound:

-   -   either in liquid form, for example by spraying a solution or        suspension containing it;    -   or in solid form, for example by sieving a powder containing it.

For the purposes of the present invention, the term “dressing” isintended to denote all types of dressings used for the treatment ofwounds. Typically, a dressing comprises at least one adhesive ornonadhesive layer or matrix.

The layer or surface which comes into contact with the wound may consistof any material or combination of materials normally used for thispurpose in the dressings field. Among these materials, mention may bemade of absorbent foams, in particular polyurethane-based hydrophilicfoams; textile materials, in particular nonwovens based on absorbent orsuperabsorbent fibers; hydrogels; or a combination of these materials;an absorbent or nonabsorbent adhesive material; an adherent ornonadherent interface structure.

Generally, the galenic or the structure of the dressing may be adjustedin order to obtain a specific release profile for the bacterium, whichis rapid or delayed, as required.

Thus, the bacterium (or a composition according to the inventioncontaining it) may be integrated into any type of existing dressing,such as, without these examples being limiting:

-   -   alginates such as, by way of examples, the products sold under        the names Urgosorb® by Laboratoires Urgo or Melgisorb® by        Molnlycke;    -   hydrocellular products such as, by way of example, the products        sold under the names Urgotul Absorb® by Laboratoires Urgo or        Tielle by Systagenix;    -   hydrocolloid dressings such as, by way of examples, the products        sold under the names Algoplaque® by Laboratoires Urgo and        Comfeel® by Coloplast;    -   hydrogels such as, by way of example, the products sold under        the names Urgo Hydrogel® by Laboratoires Urgo and Intrasite Gel®        by Smith & Nephew;    -   liquid dressings such as, by way of example, the products sold        under the names Urgo Crevasses by Laboratoires Urgo or Nexcare®        by 3M.

Of course, the amount of bacterium or bacteria used in the galenicformulation or in the dressing will be adjusted according to the desiredkinetics and also the specific constraints related to its nature,solubility, heat resistance, etc.

In the context of its use in a dressing component, the bacterium orbacteria according to the invention will be incorporated in an amountsuch that the amount of bacteria released to into the wound exudates isbetween 0.001 g/l and 50 g/l, and preferably between 0.01 and 10 g/l.

According to the galenics chosen, the use of the dressing may requireprior impregnation or hydration of the dressing with a solution, forinstance physiological saline, in order to activate the antagonisticbacteria.

The composition according to the invention may comprise one or moreantagonistic strains, optionally combined with at least one compoundchosen from probiotics, prebiotics and yeasts. Among the prebiotics,mention may be made, by way of example, of fructans such as inulin,fructooligosaccharides or trans-galactooligosaccharides, or elselong-chain or branched-chain sugars.

The bacterium according to the invention may also be combined withactive agents in particular chosen from antifungal agents, painkillers,anti-inflammatories, agents which promote healing, moisturizing agents,keratolytic agents, restructuring active agents, and anesthetics.

In particular, the active agents which can be introduced into thecomposition according to the invention may be chosen from:

-   -   antifungal agents such as polyenes, nystatin, amphotericin B,        natamycin, imidazole compounds (miconazole, ketoconazole,        clotrimazole, econazole, bifonazole, butoconazole,        fenticonazole, isoconazole, oxiconazole, sertaconazole,        sulconazole, thiabendazole, tioconazole), triazole compounds        (fluconazole, itraconazole, ravuconazole, posaconazole,        voriconazole), allylamines, terbinafine, amorolfine, naftifine,        or butenafine;    -   flucytosine (antimetabolite), griseofulvin, caspofungin or        micafungin;    -   painkillers such as paracetamol, codeine, dextropropoxyphene,        tramadol, morphine and its derivatives, corticoids and        derivatives;    -   anti-inflammatories such as glucocorticoids, non-steroidal        anti-inflammatories, aspirin, ibuprofen, ketoprofen,        flurbiprofen, diclofenac, aceclofenac, ketorolac, meloxicam,        piroxicam, tenoxicam, naproxene, indomethacin, naproxcinod,        nimesulide, celecoxib, etoricoxib, parecoxib, rofecoxib,        valdecoxib, phenylbutazone, niflumic acid or mefenamic acid;    -   active agents which promote healing, such as retinol, vitamin A,        vitamin E, N-acetyl-hydroxyproline, Centella asiatica extracts,        papain, silicones, thyme, niaouli, rosemary to and sage        essential oils, hyaluronic acid, synthetic polysulfated        oligosaccharides having 1 to 4 monosaccharide units, such as        sucrose octasulfate potassium salt, sucrose octasulfate silver        salt or sucralfate, or allantoin;    -   moisturizing agents such as hyaluronic acid, urea, glycerol,        fatty acids, aquaporin modulators, vegetable oils, chitosan,        certain sugars, including sorbitol, butters and waxes;    -   keratolytic agents such as salicylic acid, zinc salicylate,        ascorbic acid, alpha-hydroxy acids (glycolic acid, lactic acid,        malic acid, citric acid, tartaric acid), silver maple, sour        cherry or tamarind extracts, urea, the topical retinoid        Keratoline® (Sederma), proteases obtained by fermentation of        Bacillus subtilis, or the product Linked-Papain® (SACI-CFPA);    -   restructuring active agents (for example, restructuring active        agents for superficial body growths), such as silica        derivatives, vitamin E, chamomile, calcium, horsetail extract or        silk lipester;    -   anesthetics such as benzocaine, lidocaine, dibucaine, pramoxine        hydrochloride, bupivacaine, mepivacaine, prilocaine, or        etidocaine.

By way of illustration and without any limiting nature, various examplesof use of the bacteria according to the invention will be given whichmake it possible to demonstrate the antibacterial activities of theantagonist strains according to the invention.

FIG. 1 represents the inhibition halos observed after contact of thebacteria according to the invention with pathogenic bacteria on agarmedium after 48 hours of incubation.

FIG. 2 represents an inhibition halo formed after contact with thebacteria according to the invention, incorporated into a dressing, withpathogenic bacteria on agar medium after 48 hours of incubation.

FIG. 3 represents the capacity of the bacteria according to theinvention to adhere on reconstituted epidermises (as amount of bacteriaadhered in CFU/cm²).

FIG. 4 represents the results of tests for competition of adhesion oncollagen surfaces of the bacteria according to the invention withrespect to S. aureus (amount of S. aureus adhered after 24 h ofincubation (CFU/cm²)).

FIG. 5 represents the results of the tests for exclusion on collagensurfaces of the bacteria according to the invention with respect to S.aureus (amount of S. aureus after 24 h of incubation (CFU/cm²)).

FIG. 6 represents the results of the tests for competition of adhesionon collagen surfaces of the bacteria according to the invention withrespect to P. aeruginosa (amount of P. aeruginosa adhered after 24 h ofincubation (CFU/cm²)).

FIG. 7 represents the results of the tests for exclusion on collagensurfaces of the bacteria according to the invention with respect to P.aeruginosa (amount of P. aeruginosa after 24 h of incubation (CFU/cm²)).

FIGS. 8 a and 8 b represent the amount of TNF-α released (pg/ml) bymacrophages after 3.5 hours of contact with the bacteria according tothe invention, without or with stimulation by LPS from E. coli O127:B8.

EXAMPLE 1 Antimicrobial Activities of the Bacterial StrainsLactobacillus saniviri F3C5p (CNCM I-4650), Lactobacillus salivariusF50C2p (CNCM I-4651), Lactobacillus salivarius F52C3p (CNCM I-4652),Lactobacillus salivarius F41C3p (CNCM I-4653). Streptococcus mitis F3C2v(CNCM I-4654) and Lactobacillus pentosus or plantarum L1C1 (CNCM I-4655)

The Lactobacillus saniviri F3C5p (CNCM I-4650), Lactobacillus salivariusF50C2p, F52C3p and F41C3p (respectively CNCM I-4651, CNCM I-4652 andCNCM I-4653), Streptococcus mitis F3C2v (CNCM I-4654) and Lactobacilluspentosus or plantarum L1C1 (CNCM I-4655) bacteria were cultured in ManRogosa Sharpe (MRS) medium for 16 hours, at 37° C. and under anaerobicconditions. Drops of 10 μl of these cultures were deposited at thesurface of Tryptic Soy Agar (TSA) media preinoculated in the body of theagar media with 10⁶ to 10⁷ cells of methicillin-resistant Staphylococcusaureus (MRSA) ATCC 43300 or Pseudomonas aeruginosa ATCC 9027 orBacteroides fragilis ATCC 23745 or Enterobacter cloacae CIP 105132 orEnterococcus faecium ATCC 700221 or Proteus mirabilis CIP 107283 orStreptococcus pyogenes ATCC 19615 or Staphylococcus epidermidis ATCC14990 or Propionibacterium acnes ATCC 6919 or Candida albicans ATCC10231 or Malassezia furfur ATCC 14521, per ml of agar medium.

A negative control was carried out by depositing 10 μl of sterile MRSmedium.

The plates were incubated under anaerobic conditions at 37° C. for 24and 48 hours. After incubation, the diameter of the inhibition halosformed around the drops (in mm) was measured.

The results of this experiment are shown in table 1.

The sign “−” indicates an absence of inhibition halo, a sign “+”indicates an inhibition halo with a diameter of less than 1 mm, a sign“++” indicates an inhibition halo with a diameter of between 1 mm and 3mm and a sign “+++” indicates an inhibition halo with a diameter ofgreater than 3 mm No inhibition halo was demonstrated with the negativecontrol Inhibition halos were observed with the 3 strains of bacteriatested (cf. FIG. 1).

TABLE 1 Results of the tests of antimicrobial activity of the strainsLactobacillus saniviri F3C5p (CNCM I-4650), Lactobacillus salivariusF50C2p (CNCM I-4651), Lactobacillus salivarius F52C3p (CNCM I-4652),Lactobacillus salivarius F41C3p (CNCM I-4653), Streptococcus mitis F3C2v(CNCM I-4654) and Lactobacillus pentosus or plantarum L1C1 (CNCM I-4655)Staphy- lococcus Propioni- S. P. B. E. P. E. S. epider- bacteriumCandida Malassezia aureus aeruginosa fragilis cloacae mirabilis faeciumpyogenes midis acnes albicans furfur ATCC ATCC ATCC CIP CIP ATCC ATCCATCC ATCC ATCC ATCC Strains 43300 9027 23745 105132 107283 700221 1961514990 6919 10231 14521 L. saniviri +++ + +++ ++ ++ +++ +++ +++ +++ + +++F3C5p (CNCM I-4650) L. salivarius ++ + ++ + + ++ +++ +++ +++ − − F50C2p(CNCM I-4651) L. salivarius ++ ++ ++ + ++ ++ +++ +++ +++ − − F52C3p(CNCM I-4652) L. salivarius + − − + + − +++ ++ +++ − − F41C3p (CNCMI-4653) S. mitis ++ − +++ − ++ +++ ++ − +++ − ++ F3C2v (CNCM I-4654)Lactobacillus + − ++ + + + ++ + +++ − − sp. L1C1 (CNCM I-4655)

EXAMPLE 2 Antimicrobial Activities of the Bacterial StrainsLactobacillus saniviri F3C5p (CNCM I-4650), Lactobacillus salivariusF50C2p (CNCM I-4651), Lactobacillus salivarius F52C3p (CNCM I-4652),Lactobacillus salivarius F41C3p (CNCM I-4653), Streptococcus mitis F3C2v(CNCM I-4654) and Lactobacillus pentosus or plantarum L1C1 (CNCM I-4655)after Incorporation into a Dressing

The F3C5p, F50C2p, F52C3p, F41C3p, F3C2v and L1C1 bacteria were culturedin Man Rogosa Sharpe (MRS) medium for 16 hours, at 37° C. and underanaerobic conditions. Pieces of dressings (1 cm×1 cm) composed ofpolyurethane foam and of a lipido-colloid mesh were impregnated with 500μl of the culture of bacteria according to the invention (concentrationof between 10⁹ and 10¹⁰ CFU.ml⁻¹) and deposited at the surface ofTryptic Soy Agar (TSA) media preinoculated in the body of the agar mediawith 10⁶ to 10⁷ cells of Staphylococcus aureus MRSA ATCC 43300 orPseudomonas aeruginosa ATCC 9027. A negative control was carried out bydepositing 500 μl of sterile MRS medium.

The plates were incubated under anaerobic conditions at 37° C. for 24and 48 hours. After incubation, the antimicrobial activity isdemonstrated by the presence of an inhibition halo. After incubation,the inhibition halos are visible around the dressings impregnated withthe bacteria Lactobacillus saniviri F3C5p, Lactobacillus salivariusF50C2p, Lactobacillus salivarius F52C3p, Lactobacillus salivariusF41C3p, Streptococcus mitis F3C2v and Lactobacillus pentosus orplantarum L1C1 (cf. FIG. 2). No inhibition halo is visible around thedressings impregnated with the MRS medium.

EXAMPLE 3 Capacities of the Strains According to the Invention to Adhereon Collagen

Tests for adhesion of the Lactobacillus saniviri F3C5p, Lactobacillussalivarius F50C2p, Lactobacillus salivarius F52C3p, Lactobacillussalivarius F41C3p, Streptococcus mitis F3C2v and Lactobacillus pentosusor plantarum L1C1 bacteria were carried out on reconstituted epidermisesof EpiSkin (SkinEthic) type (1.07 cm²) aged 13 days. The insertscontaining the epidermises were placed in a 12-well plate with 2 ml ofmaintenance medium and incubated for 24 hours at 35° C.±2° C. in orderto regenerate the epidermises. After incubation, the maintenance mediumwas removed and 2 ml of MRS medium were added. A medium simulating woundexudates, called Simulated Wound Fluid (50/50 vol/vol) (described inWerthén et al., 2010) was then inoculated with the bacteria according tothe invention (concentration of approximately 2.5×10⁷ CFU.ml⁻¹). After24 h of incubation, the bacteria which had not adhered were removed bywashing with physiological saline. The epidermises were detached fromthe inserts with a scalpel and placed in a sterile container containing9 ml of MRS medium. The bacteria that had adhered were detached bymechanical action (ultrasonic bath) and counted by dilution-plating onagar medium.

The Lactobacillus saniviri F3C5p, Lactobacillus salivarius F50C2p,Lactobacillus salivarius F52C3p, Lactobacillus salivarius F41C3p,Streptococcus mitis F3C2v and Lactobacillus pentosus or plantarum L1C1bacteria are capable of adhering to the epidermis and of persisting for24 hours. The Lactobacillus saniviri F3C5p strain exhibits the greatestadhesion capacity (cf. FIG. 3).

EXAMPLE 4 Barrier Effect—Inhibition of Pathogen Adhesion on a CollagenSurface

The capacity of the Lactobacillus saniviri F3C5p, Lactobacillussalivarius F50C2p, Lactobacillus salivarius F52C3p, Lactobacillussalivarius F41C3p, Streptococcus mitis F3C2v and Lactobacillus pentosusor plantarum L1C1 bacterial strains to limit and/or inhibit the adhesionof pathogenic species (S. aureus MRSA ATCC 43300 or P. aeruginosa ATCC9027) on matrices containing collagen was evaluated. The tests werecarried out in 24-well microplates coated with type I collagen (BDBiocoat™ Collagen I).

The pathogenic bacteria were cultured for 16 hours at 37° C. in TrypticSoy Broth (TSB) medium. After incubation, the cultures were diluted inTSB medium to concentrations of approximately 2.5×10⁷ CFU.ml⁻¹, 2.5×10⁵CFU.ml⁻¹ and 2.5×10³ CFU.ml⁻¹.

The Lactobacillus saniviri F3C5p, Lactobacillus salivarius F50C2p,Lactobacillus salivarius F52C3p, Lactobacillus salivarius F41C3p,Streptococcus mitis F3C2v and Lactobacillus pentosus or plantarum L1C1bacteria were cultured in Man Rogosa Sharpe (MRS) medium for 16 hours,at 37° C. and under anaerobic conditions.

For the adhesion competition tests, the F3C5p, F50C2p and F52C3pbacteria and the pathogenic bacterium (S. aureus or P. aeruginosa) weresimultaneously added at a respective concentration of approximately2.5×10⁷ CFU.ml⁻¹ and 2.5×10⁷ CFU.ml⁻¹ or 2.5×10⁵ CFU.ml⁻¹ or 2.5×10³CFU.ml⁻¹ for the pathogenic bacterium. The F41C3p, F3C2v and L1C1bacteria and the pathogenic bacterium (S. aureus or P. aeruginosa) weresimultaneously added at a respective concentration of approximately2.5×10⁷ CFU.ml⁻¹ and 2.5×10⁷ CFU.ml⁻¹.

For the exclusion tests, the F3C5p, F50C2p and F52C3p bacteria wereintroduced into the wells at a concentration of approximately 2.5×10⁷CFU.ml⁻¹ and incubated at 37° C. for 24 hours. After adhesion, the wellswere washed with physiological saline and the pathogenic strain (S.aureus or P. aeruginosa) was introduced into the wells at concentrationsof approximately 2.5×10⁷ CFU.ml⁻¹ or 2.5×10⁵ CFU.ml⁻¹ or 2.5×10³CFU.ml⁻¹. The F41C3p, F3C2v and L1C1 bacteria were tested at aconcentration of approximately 2.5×10⁷ CFU.ml⁻¹ with the pathogenicstrain (S. aureus or P. aeruginosa) at a concentration of approximately2.5×10⁷ CFU.ml⁻¹.

For each of the tests, after 24 hours of contact, the pathogenicbacteria were specifically counted on Baird-Parker medium supplementedwith an emulsion of egg yolk containing potassium tellurite for S.aureus or cephalosporin/fucidin/cetrimide (CFC) medium for P.aeruginosa. After 24 h of incubation at 35° C.±2° C., the characteristiccolonies were counted. A nontreated control with the bacteria accordingto the invention was carried out for each of the tests.

The F3C5p, F50C2p, F52C3p, F41C3p, F3C2v and L1C1 bacteria make itpossible to strongly limit the adhesion of S. aureus and thecolonization of the collagen-coated substrate compared with thenontreated control for the three concentrations tested (cf. FIGS. 4 and5).

The F3C5p, F50C2p, F52C3p, F41C3p, F3C2v and L1C1 bacteria make itpossible to limit the adhesion of P. aeruginosa and the colonization ofthe collagen-coated substrate compared with the nontreated control whenthe initial contamination is less than 10⁵ CFU/cm² (cf. FIGS. 6 and 7).

EXAMPLE 5 Immunomodulatory Activities on Macrophages

The Lactobacillus saniviri F3C5p, Lactobacillus salivarius F50C2p,Lactobacillus salivarius F52C3, Lactobacillus pentosus/plantarum L1C1,Lactobacillus salivarius F41C3p and Streptococcus mitis F3C2v strainswere cultured in Man Rogosa Sharpe (MRS) medium for 16 hours, at 37° C.and under anaerobic conditions. The bacteria were recovered bycentrifugation and then ultrasound-inactivated or heat-inactivated (95°C.) in order to obtain bacterial extracts.

THP1 monocyte cells (ATCC TIB-202) were cultured in Roswell ParkMemorial Institute (RPMI) medium and were differentiated to macrophagesby addition of phorbol-12-myristate-13-acetate (PMA). After 24 hours ofculture, the macrophages obtained were exposed (i) either to thebacterial extracts alone, (ii) or to LPS from E. coli O127:B8, (iii) orto LPS from E. coli O127:B8 in the presence of cell extract. After 3.5hours of contact, the concentration of tumor necrosis factor (TNF-α) wasmeasured in the culture supernatant using an ELISA method.

The addition of the bacterial extracts alone does not induce anysignificant release of TNF-α compared with the control not containingcell extract and therefore does not induce any pro-inflammatoryreaction, with the exception of the L1C1 strain, which induces a weakrelease of TNF-α (concentration of 121 pg/ml).

The stimulation of the macrophages with the LPS from E. coli bringsabout a considerable release of TNF-α in the absence of bacterialextracts (concentration about 500 pg/ml). The simultaneous addition ofthe cell extracts prepared from the various bacterial strains (F3C5p,F41C3p, F50C2p, F52C3p, L1C1 or F3C2v) with the LPS makes it possible tosignificantly reduce (by a factor of 2 to 5) the release of TNF-α by themacrophages. These results demonstrate the anti-inflammatory potentialof the 6 strains of lactic acid bacteria.

The references cited in the present application are the following:

-   1 Brachkova M I, Marques P, Rocha J, Sepodes B, Duarte M A, Pinto J    F (2011). Alginate films containing Lactobacillus plantarum as wound    dressing for prevention of burn infection. J. Hosp. Infect. 79:    375-377-   2 Costerton, J. W., Stewart, P. S. and Greenberg, E. P. (1999).    Bacterial biofilms: a common cause of persistent infections. Science    284 (5418): 1318-1322-   3 Gan B S, Kim J, Reid G, Cadieux P, Howard J C (2002).    Lactobacillus fermentum RC-14 inhibits Staphylococcus aureus    infection of surgical implants in rats. J. Infect. Dis. 185:    1369-1372-   4 Gueniche A, Hennino A, Goujon C, Dahel K, Bastien P, Martin R,    Jourdain R, Breton L (2006) Improvement of atopic dermatitis skin    symptoms by Vitreoscilla filiformis bacterial extract. Eur. J.    Dermatol. 16: 380-384-   5 Gueniche A, Buetler T, Benyacoub J, Blum S (2008a). Lactobacillus    johnsonii provides a dose-dependent protection against UVR-induced    immunosuppression. Eur. J. Dermatol. 18: 476-477-   6 Gueniche A, Cathelineau A C, Bastien P, Esdaile J, Martin R,    Queille Roussel C, Breton L (2008b). Vitreoscilla filiformis biomass    improves seborrheic dermatitis. J. Eur. Acad. Dermatol. Venereol.    22: 1014-1015-   7 Gueniche A, Dahel K, Bastien P, Martin R, Nicolas J F, Breton L    (2008c). Vitreoscilla filiformis bacterial extract to improve the    efficacy of emollient used in atopic dermatitis symptoms. J. Eur.    Acad. Dermatol. Venereol. 22: 746-747-   8 Gueniche A, Knaudt B, Schuck E, Volz T, Bastien P, Martin R,    Rocken M, Breton L, Biedermann T (2008d). Effects of nonpathogenic    gram-negative bacterium Vitreoscilla filiformis lysate on atopic    dermatitis: a prospective, randomized, double-blind,    placebo-controlled clinical study. Br. J. Dermatol. 159: 1357-1363-   9 Gueniche A, Bastien P, Ovigne J M, Kermici M, Courchay G,    Chevalier V, Breton L, Castiel-Higounenc I (2009). Bifidobacterium    longum lysate, a new ingredient for reactive skin. Exp. Dermatol.    19: e1-8-   10 Gueniche A, Benyacoub J, Philippe D, Bastien P, Kusy N, Breton L,    Blum S, Castiel-Higounenc I (2010). Lactobacillus paracasei CNCM    I-2116 (ST11) inhibits substance P-induced skin inflammation and    accelerates skin barrier function recovery in vitro. Eur. J.    Dermatol. 20: 731-737-   11 Halper J, Leshin L S, Lewis S J, Li W I (2003). Wound healing and    angiogenic properties of supernatants from Lactobacillus cultures.    Exp Biol Med 228: 1329-1337-   12 Oh S, Kim S H, Ko Y, Sim J H, Kim K S, Lee S H, Park S, Kim Y J    (2006). Effect of bacteriocin produced by Lactococcus sp. H Y 449 on    skin-inflammatory bacteria. Food and Chemical Toxicology 44 (2006)    1184-1190-   13 Im E, Choi Y J, Kim C H, Fiocchi C, Pothoulakis C, Rhee S H    (2009). The angiogenic effect of probiotic Bacillus polyfermenticus    on human intestinal microvascular endothelial cells is mediated by    IL-8. Am. J. Physiol. Gastrointest. Liver Physiol. 297: G999-G1008-   14 Mi-Sun Kang M S, Oh J S, Lee S W, Lim H S, Choi N K, and Kim S M    (2012). Effect of Lactobacillus reuteri on the proliferation of    Propionibacterium acnes and Staphylococcus epidermidis. The Journal    of Microbiology (2012) Vol. 50, No. 1, pp. 137-142-   15 Peral M C, Martinez M A, Valdez J C (2009). Bacteriotherapy with    Lactobacillus plantarum in burns. Int. Wound J. 6: 73-81-   16 Peral M C, Rachid M M, Gobbato N M, Huaman Martinez M A, Valdez J    C (2010). Interleukin-8 production by polymorphonuclear leukocytes    from patients with chronic infected leg ulcers treated with    Lactobacillus plantarum. Clin. Microbiol. Infect. 16: 281-286-   17 Ramos A N, Gobbato N, Rachid M, Gonzalez L, Yantorno O, Valdez J    C (2010). Effect of Lactobacillus plantarum and Pseudomonas    aeruginosa culture supernatants on polymorphonuclear damage and    inflammatory response. Int. Immunopharmacol. 10: 247-251-   18 Sikorska H, Smoragiewiczb W (2013). Role of probiotics in the    prevention and treatment of meticillin-resistant Staphylococcus    aureus infections. International Journal of Antimicrobial Agents    42 (2013) 475-481-   19 Valdez J C, Peral M C, Rachid M, Santana M, Perdigon G (2005).    Interference of Lactobacillus plantarum with Pseudomonas aeruginosa    in vitro and in infected burns: the potential use of probiotics in    wound treatment. Clin. Microbiol. Infect. 11: 472-479-   20 Alberto N. Ramos, Maria E. Sesto Cabral, Diego Noseda, Alejandra    Bosch, Osvaldo M. Yantorno, Juan C. Valdez, (2012). Antipathogenic    properties of Lactobacillus plantarum on Pseudomonas aeruginosa: The    potential use of its supernatants in the treatment of infected    chronic wounds. Wound Rep Reg (2012)

1. A bacterium chosen from Lactobacillus saniviri registered on Jul. 12,2012, at the CNCM under No. I-4650, Lactobacillus salivarius registeredon Jul. 12, 2012, at the CNCM respectively under Nos. I-4651, I-4652 andI-4653, Streptococcus mitis registered on Jul. 12, 2012, under No. CNCMI-4654 and Lactobacillus pentosus or plantarum registered on Jul. 12,2012, under No. CNCM I-4655.
 2. The bacterium as claimed in claim 1, foruse as an active ingredient, a medical device, a cosmetic or a foodsupplement or as an active ingredient in a medicament, in a medicaldevice, in a cosmetic or in a food supplement.
 3. The bacterium asclaimed in claim 1, for use in preventing and/or treating an infectionand/or a colonization related to at least one bacterium or one yeastchosen from S. aureus, P. aeruginosa, Streptococcus pyogenes,Enterococcus faecium, Enterobacter cloacae, Proteus mirabilis,Bacteroides fragilis, Staphylococcus epidermidis, Propionibacteriumacnes, Candida albicans and Malassezia furfur.
 4. The bacterium asclaimed in claim 1, for use in preventing and/or treating an infectionand/or a colonization related to S. aureus and/or P. aeruginosa.
 5. Thebacterium as claimed in claim 1, for use as an immunomodulator.
 6. Thebacterium as claimed in claim 1, characterized in that it is applied tothe skin, wounds, mucosae and/or superficial body growths.
 7. Thebacterium as claimed in claim 3, characterized in that the infectionand/or the colonization concern the skin, a wound, in particular a woundchosen from diabetic foot ulcers, leg ulcers of arterial origin, legulcers of venous origin, bedsores, whitlow, acute wounds, traumaticwounds and post-operative wounds.
 8. A composition comprising at leastone bacterium as claimed in claim
 1. 9. The composition as claimed inclaim 8, characterized in that it also comprises at least one compoundchosen from probiotics, prebiotics and yeasts.
 10. The composition asclaimed in claim 8, characterized in that it also comprises at least oneactive agent chosen from antifungal agents, painkillers,anti-inflammatories, active agents which promote healing, moisturizingagents, keratolytic agents, restructuring agents and anesthetics. 11.The composition as claimed in claim 8, characterized in that it issuitable for topical, oral or parenteral application.
 12. Thecomposition as claimed in claim 8, characterized in that it is in theform of a salve, a cream, a milk, an ointment, a powder, an impregnatedpad, a syndet, a wipe, a solution, a gel, a spray, a foam, a suspension,a lotion, a stick, a shampoo, a washing base, a tablet, a gel capsule, afood product or an injectable solution.
 13. The composition as claimedin claim 8, characterized in that the bacterium is present in an amountof between 10³ and 10¹² bacteria.
 14. The composition as claimed inclaim 8, characterized in that the bacterium is present in the form ofan inactivated cell, a living cell or a cell lysate, which may beencapsulated or nonencapsulated, immobilized or nonimmobilized andlyophilized or nonlyophilized.
 15. A dressing comprising at least onebacterium as claimed in claim 1.